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Influence of aging and neurodegeneration on dendritic spine morphology

  • Review Article
  • Published:
Translational Neuroscience

Abstract

In neuronal circuits, excitatory synaptic transmission predominantly occurs at postsynaptic protrusions called dendritic spines. Spines are highly plastic structures capable of formation, enlargement, shrinkage, and elimination over time. Individual spine morphology is widely variable, and evidence suggests these differences in morphology are relevant to spine function. Recent reports provide evidence that spine structural plasticity underlies functional synaptic changes, including those seen in animal models of learning and memory plasticity. Conversely, impairments in cognitive functions, such as those commonly seen in aging, have recently been linked to and correlated with alterations in spine density and morphology. In addition, dendritic spine density and morphology also appear to be altered in various transgenic animal models of neurodegenerative diseases. Ultimately, an understanding of the synaptic basis of age- and disease-related cognitive impairments may lead to the development of drug treatments that can restore or protect synaptic profiles in neural circuits that mediate cognition.

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Abbreviations

AMPA:

α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid

NMDA:

N-methyl-D-aspartate

SSTEM:

serial section transmission electron microscopy

PP:

perforant path

DNMS:

delayed nonmatching-to-sample

EM:

electron microscopy

AD:

Alzheimer’s disease

HD:

Huntington’s disease

PD:

Parkinson’s disease

DA:

dopamine

MSN:

medium spiny neuron

DLB:

dementia with Lewy bodies

CJD:

Creutzfeldt-Jakob disease

PrP:

prion protein

Aβ:

amyloid beta protein

CDR:

clinical dementia rating

APP:

amyloid precursor protein

References

  1. Harris KM, Stevens JK: Dendritic spines of rat cerebellar purkinje cells: Serial electron microscopy with reference to their biophysical characteristics. J Neurosci 1988;8:4455–4469.

    PubMed  CAS  Google Scholar 

  2. Nimchinsky EA, Sabatini BL, Svoboda K: Structure and function of dendritic spines. Annu Rev Physiol 2002;64:313–353.

    Article  PubMed  CAS  Google Scholar 

  3. Sorra KE, Harris KM: Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 2000;10:501–511.

    Article  PubMed  CAS  Google Scholar 

  4. Bhatt DH, Zhang S, Gan WB: Dendritic spine dynamics. Annu Rev Physiol 2009;71:261–282.

    Article  PubMed  CAS  Google Scholar 

  5. Holtmaat A, Bonhoeffer T, Chow DK, Chuckowree J, De Paola V, Hofer SB, Hubener M, Keck T, Knott G, Lee WC, Mostany R, Mrsic-Flogel TD, Nedivi E, Portera-Cailliau C, Svoboda K, Trachtenberg JT, Wilbrecht L: Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc 2009;4:1128–1144.

    Article  PubMed  CAS  Google Scholar 

  6. Peters A, Kaiserman-Abramof IR: The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. Am J Anat 1970;127:321–355.

    Article  PubMed  CAS  Google Scholar 

  7. Grutzendler J, Kasthuri N, Gan WB: Long-term dendritic spine stability in the adult cortex. Nature 2002;420:812–816.

    Article  PubMed  CAS  Google Scholar 

  8. Harris KM, Stevens JK: Dendritic spines of ca 1 pyramidal cells in the rat hippocampus: Serial electron microscopy with reference to their biophysical characteristics. J Neurosci 1989;9:2982–2997.

    PubMed  CAS  Google Scholar 

  9. Holtmaat AJ, Trachtenberg JT, Wilbrecht L, Shepherd GM, Zhang X, Knott GW, Svoboda K: Transient and persistent dendritic spines in the neocortex in vivo. Neuron 2005;45:279–291.

    Article  PubMed  CAS  Google Scholar 

  10. Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K: Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 2002;420:788–794.

    Article  PubMed  CAS  Google Scholar 

  11. Yasumatsu N, Matsuzaki M, Miyazaki T, Noguchi J, Kasai H: Principles of long-term dynamics of dendritic spines. J Neurosci 2008;28:13592–13608.

    Article  PubMed  CAS  Google Scholar 

  12. Yang G, Pan F, Gan WB: Stably maintained dendritic spines are associated with lifelong memories. Nature 2009;462:920–924.

    Article  PubMed  CAS  Google Scholar 

  13. Kasai H, Matsuzaki M, Noguchi J, Yasumatsu N, Nakahara H: Structurestability-function relationships of dendritic spines. Trends Neurosci 2003;26:360–368.

    Article  PubMed  CAS  Google Scholar 

  14. Matsuzaki M, Ellis-Davies GC, Nemoto T, Miyashita Y, Iino M, Kasai H: Dendritic spine geometry is critical for ampa receptor expression in hippocampal ca1 pyramidal neurons. Nat Neurosci 2001;4:1086–1092.

    Article  PubMed  CAS  Google Scholar 

  15. Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H: Structural basis of long-term potentiation in single dendritic spines. Nature 2004;429:761–766.

    Article  PubMed  CAS  Google Scholar 

  16. Takumi Y, Ramirez-Leon V, Laake P, Rinvik E, Ottersen OP: Different modes of expression of ampa and nmda receptors in hippocampal synapses. Nat Neurosci 1999;2:618–624.

    Article  PubMed  CAS  Google Scholar 

  17. Leuner B, Shors TJ: New spines, new memories. Mol Neurobiol 2004;29:117–130.

    Article  PubMed  CAS  Google Scholar 

  18. Segal M: Dendritic spines and long-term plasticity. Nat Rev Neurosci 2005;6:277–284.

    Article  PubMed  CAS  Google Scholar 

  19. Lamprecht R, LeDoux J: Structural plasticity and memory. Nat Rev Neurosci 2004;5:45–54.

    Article  PubMed  CAS  Google Scholar 

  20. Leuner B, Falduto J, Shors TJ: Associative memory formation increases the observation of dendritic spines in the hippocampus. J Neurosci 2003;23:659–665.

    PubMed  CAS  Google Scholar 

  21. Knafo S, Grossman Y, Barkai E, Benshalom G: Olfactory learning is associated with increased spine density along apical dendrites of pyramidal neurons in the rat piriform cortex. Eur J Neurosci 2001;13:633–638.

    Article  PubMed  CAS  Google Scholar 

  22. Knafo S, Ariav G, Barkai E, Libersat F: Olfactory learning-induced increase in spine density along the apical dendrites of ca1 hippocampal neurons. Hippocampus 2004;14:819–825.

    Article  PubMed  Google Scholar 

  23. Restivo L, Roman FS, Ammassari-Teule M, Marchetti E: Simultaneous olfactory discrimination elicits a strain-specific increase in dendritic spines in the hippocampus of inbred mice. Hippocampus 2006;16:472–479.

    Article  PubMed  Google Scholar 

  24. Restivo L, Roman F, Dumuis A, Bockaert J, Marchetti E, Ammassari-Teule M: The promnesic effect of g-protein-coupled 5-ht4 receptors activation is mediated by a potentiation of learning-induced spine growth in the mouse hippocampus. Neuropsychopharmacology 2008;33:2427–2434.

    Article  PubMed  CAS  Google Scholar 

  25. Restivo L, Vetere G, Bontempi B, Ammassari-Teule M: The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex. J Neurosci 2009;29:8206–8214.

    Article  PubMed  CAS  Google Scholar 

  26. Fiala JC, Spacek J, Harris KM: Dendritic spine pathology: Cause or consequence of neurological disorders? Brain Res Rev 2002;39:29–54.

    Article  PubMed  Google Scholar 

  27. Geinisman Y, de Toledo-Morrell L, Morrell F: Loss of perforated synapses in the dentate gyrus: Morphological substrate of memory deficit in aged rats. Proc Natl Acad Sci U S A 1986;83:3027–3031.

    Article  PubMed  CAS  Google Scholar 

  28. Geinisman Y, de Toledo-Morrell L, Morrell F: Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory. Brain Res 1986;398:266–275.

    Article  PubMed  CAS  Google Scholar 

  29. Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR: Agerelated dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb Cortex 2003;13:950–961.

    Article  PubMed  Google Scholar 

  30. Hao J, Rapp PR, Janssen WG, Lou W, Lasley BL, Hof PR, Morrison JH: Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex. Proc Natl Acad Sci U S A 2007;104:11465–11470.

    Article  PubMed  CAS  Google Scholar 

  31. Hara Y, Park CS, Janssen WG, Roberts MT, Morrison JH, Rapp PR: Synaptic correlates of memory and menopause in the hippocampal dentate gyrus in rhesus monkeys. Neurobiol Aging 2010

  32. Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WG, Lou W, Rapp PR, Morrison JH: Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 2010;30:7507–7515.

    Article  PubMed  CAS  Google Scholar 

  33. Lanz TA, Carter DB, Merchant KM: Dendritic spine loss in the hippocampus of young pdapp and tg2576 mice and its prevention by the apoe2 genotype. Neurobiol Dis 2003;13:246–253.

    Article  PubMed  CAS  Google Scholar 

  34. Spires TL, Meyer-Luehmann M, Stern EA, McLean PJ, Skoch J, Nguyen PT, Bacskai BJ, Hyman BT: Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 2005;25:7278–7287.

    Article  PubMed  CAS  Google Scholar 

  35. Rocher AB, Kinson MS, Luebke JI: Significant structural but not physiological changes in cortical neurons of 12-month-old tg2576 mice. Neurobiol Dis 2008;32:309–318.

    Article  PubMed  CAS  Google Scholar 

  36. Rocher AB, Crimins JL, Amatrudo JM, Kinson MS, Todd-Brown MA, Lewis J, Luebke JI: Structural and functional changes in tau mutant mice neurons are not linked to the presence of nfts. Exp Neurol 2009;223:385–393.

    Article  PubMed  CAS  Google Scholar 

  37. Knafo S, Alonso-Nanclares L, Gonzalez-Soriano J, Merino-Serrais P, Fernaud-Espinosa I, Ferrer I, DeFelipe J: Widespread changes in dendritic spines in a model of alzheimer’s disease. Cereb Cortex 2009;19:586–592.

    Article  PubMed  CAS  Google Scholar 

  38. Auffret A, Gautheron V, Repici M, Kraftsik R, Mount HT, Mariani J, Rovira C: Age-dependent impairment of spine morphology and synaptic plasticity in hippocampal ca1 neurons of a presenilin 1 transgenic mouse model of alzheimer’s disease. J Neurosci 2009;29:10144–10152.

    Article  PubMed  CAS  Google Scholar 

  39. Dickstein DL, Brautigam H, Stockton SD, Jr., Schmeidler J, Hof PR: Changes in dendritic complexity and spine morphology in transgenic mice expressing human wild-type tau. Brain Struct Funct 2010;214:161–179.

    Article  PubMed  Google Scholar 

  40. Shansky RM, Hamo C, Hof PR, McEwen BS, Morrison JH: Stressinduced dendritic remodeling in the prefrontal cortex is circuit specific. Cereb Cortex 2009;19:2479–2484.

    Article  PubMed  Google Scholar 

  41. Allard S, Scardochio T, Cuello AC, Ribeiro-da-Silva A: Correlation of cognitive performance and morphological changes in neocortical pyramidal neurons in aging. Neurobiol Aging 2010

  42. Feng G, Mellor RH, Bernstein M, Keller-Peck C, Nguyen QT, Wallace M, Nerbonne JM, Lichtman JW, Sanes JR: Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of gfp. Neuron 2000;28:41–51.

    Article  PubMed  CAS  Google Scholar 

  43. Wearne SL, Rodriguez A, Ehlenberger DB, Rocher AB, Henderson SC, Hof PR: New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales. Neuroscience 2005;136:661–680.

    Article  PubMed  CAS  Google Scholar 

  44. Rodriguez A, Ehlenberger DB, Hof PR, Wearne SL: Rayburst sampling, an algorithm for automated three-dimensional shape analysis from laser scanning microscopy images. Nat Protoc 2006;1:2152–2161.

    Article  PubMed  CAS  Google Scholar 

  45. Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL: Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS ONE 2008;3:e1997.

    Article  PubMed  CAS  Google Scholar 

  46. Pawley J: Fundamental limits in confocal microscopy, ed Third. New York, Springer Science, 2006.

    Google Scholar 

  47. Yang G, Pan F, Parkhurst CN, Grutzendler J, Gan WB: Thinned-skull cranial window technique for long-term imaging of the cortex in live mice. Nat Protoc 2010;5:201–208.

    Article  PubMed  CAS  Google Scholar 

  48. Xu HT, Pan F, Yang G, Gan WB: Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex. Nat Neurosci 2007;10:549–551.

    Article  PubMed  CAS  Google Scholar 

  49. Mizrahi A, Crowley JC, Shtoyerman E, Katz LC: High-resolution in vivo imaging of hippocampal dendrites and spines. J Neurosci 2004;24:3147–3151.

    Article  PubMed  CAS  Google Scholar 

  50. Rapp PR, Gallagher M: Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci U S A 1996;93:9926–9930.

    Article  PubMed  CAS  Google Scholar 

  51. Gazzaley AH, Thakker MM, Hof PR, Morrison JH: Preserved number of entorhinal cortex layer ii neurons in aged macaque monkeys. Neurobiol Aging 1997;18:549–553.

    Article  PubMed  CAS  Google Scholar 

  52. Hof PR, Nimchinsky EA, Young WG, Morrison JH: Numbers of meynert and layer ivb cells in area v1: A stereologic analysis in young and aged macaque monkeys. J Comp Neurol 2000;420:113–126.

    Article  PubMed  CAS  Google Scholar 

  53. Rapp PR, Deroche PS, Mao Y, Burwell RD: Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits. Cereb Cortex 2002;12:1171–1179.

    Article  PubMed  Google Scholar 

  54. Smith DE, Rapp PR, McKay HM, Roberts JA, Tuszynski MH: Memory impairment in aged primates is associated with focal death of cortical neurons and atrophy of subcortical neurons. J Neurosci 2004;24:4373–4381.

    Article  PubMed  CAS  Google Scholar 

  55. Hof PR, Morrison JH: The aging brain: Morphomolecular senescence of cortical circuits. Trends Neurosci 2004;27:607–613.

    Article  PubMed  CAS  Google Scholar 

  56. Gallagher M, Rapp PR: The use of animal models to study the effects of aging on cognition. Annu Rev Psychol 1997;48:339–370.

    Article  PubMed  CAS  Google Scholar 

  57. Geinisman Y, Detoledo-Morrell L, Morrell F, Heller RE: Hippocampal markers of age-related memory dysfunction: Behavioral, electrophysiological and morphological perspectives. Prog Neurobiol 1995;45:223–252.

    Article  PubMed  CAS  Google Scholar 

  58. de Brabander JM, Kramers RJ, Uylings HB: Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex. Eur J Neurosci 1998;10:1261–1269.

    Article  PubMed  Google Scholar 

  59. Jacobs B, Driscoll L, Schall M: Life-span dendritic and spine changes in areas 10 and 18 of human cortex: A quantitative Golgi study. J Comp Neurol 1997;386:661–680.

    Article  PubMed  CAS  Google Scholar 

  60. Jacobs B, Scheibel AB: A quantitative dendritic analysis of wernicke’s area in humans. I. Lifespan changes. J Comp Neurol 1993;327:83–96.

    Article  PubMed  CAS  Google Scholar 

  61. Petanjek Z, Judas M, Kostovic I, Uylings HB: Lifespan alterations of basal dendritic trees of pyramidal neurons in the human prefrontal cortex: A layer-specific pattern. Cereb Cortex 2008;18:915–929.

    Article  PubMed  Google Scholar 

  62. Peters A, Sethares C, Luebke JI: Synapses are lost during aging in the primate prefrontal cortex. Neuroscience 2008;152:970–981.

    Article  PubMed  CAS  Google Scholar 

  63. Chang YM, Rosene DL, Killiany RJ, Mangiamele LA, Luebke JI: Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. Cereb Cortex 2005;15:409–418.

    Article  PubMed  Google Scholar 

  64. Luebke JI, Chang YM: Effects of aging on the electrophysiological properties of layer 5 pyramidal cells in the monkey prefrontal cortex. Neuroscience 2007;150:556–562.

    Article  PubMed  CAS  Google Scholar 

  65. Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL: The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 2009;19:2248–2268.

    Article  PubMed  Google Scholar 

  66. Luebke JI, Weaver CM, Rocher AB, Rodriguez A, Crimins JL, Dickstein DL, Wearne SL, Hof PR: Dendritic vulnerability in neurodegenerative disease: Insights from analyses of cortical pyramidal neurons in transgenic mouse models. Brain Struct Funct 2010;214:181–199.

    Article  PubMed  Google Scholar 

  67. Baxter MG: Age-related memory impairment. Is the cure worse than the disease? Neuron 2003;40:669–670.

    Article  PubMed  CAS  Google Scholar 

  68. Venneti S: Prion diseases. Clin Lab Med; 30:293–309.

  69. Moreno JA, Mallucci GR: Dysfunction and recovery of synapses in prion disease: Implications for neurodegeneration. Biochem Soc Trans;38:482–487.

  70. Prusiner SB, Scott MR, DeArmond SJ, Cohen FE: Prion protein biology. Cell 1998;93:337–348.

    Article  PubMed  CAS  Google Scholar 

  71. Westergard L, Christensen HM, Harris DA: The cellular prion protein (prp(c)): Its physiological function and role in disease. Biochim Biophys Acta 2007;1772:629–644.

    PubMed  CAS  Google Scholar 

  72. Mallucci GR, Ratte S, Asante EA, Linehan J, Gowland I, Jefferys JG, Collinge J: Post-natal knockout of prion protein alters hippocampal ca1 properties, but does not result in neurodegeneration. Embo J 2002;21:202–210.

    Article  PubMed  CAS  Google Scholar 

  73. Mallucci G, Dickinson A, Linehan J, Klohn PC, Brandner S, Collinge J: Depleting neuronal prp in prion infection prevents disease and reverses spongiosis. Science 2003;302:871–874.

    Article  PubMed  CAS  Google Scholar 

  74. Landis DM, Williams RS, Masters CL: Golgi and electronmicroscopic studies of spongiform encephalopathy. Neurology 1981;31:538–549.

    PubMed  CAS  Google Scholar 

  75. Hogan RN, Baringer JR, Prusiner SB: Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: A quantitative Golgi analysis. J Neuropathol Exp Neurol 1987;46:461–473.

    Article  PubMed  CAS  Google Scholar 

  76. Johnston AR, Black C, Fraser J, MacLeod N: Scrapie infection alters the membrane and synaptic properties of mouse hippocampal ca1 pyramidal neurones. J Physiol 1997;500(Pt 1):1–15.

    PubMed  CAS  Google Scholar 

  77. Belichenko PV, Brown D, Jeffrey M, Fraser JR: Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice. Neuropathol Appl Neurobiol 2000;26:143–149.

    Article  PubMed  CAS  Google Scholar 

  78. Jeffrey M, Halliday WG, Bell J, Johnston AR, MacLeod NK, Ingham C, Sayers AR, Brown DA, Fraser JR: Synapse loss associated with abnormal prp precedes neuronal degeneration in the scrapie-infected murine hippocampus. Neuropathol Appl Neurobiol 2000;26:41–54.

    Article  PubMed  CAS  Google Scholar 

  79. Fuhrmann M, Mitteregger G, Kretzschmar H, Herms J: Dendritic pathology in prion disease starts at the synaptic spine. J Neurosci 2007;27:6224–6233.

    Article  PubMed  CAS  Google Scholar 

  80. Jeffrey M, Goodsir CM, Bruce ME, McBride PA, Fraser JR: In vivo toxicity of prion protein in murine scrapie: Ultrastructural and immunogold studies. Neuropathol Appl Neurobiol 1997;23:93–101.

    Article  PubMed  CAS  Google Scholar 

  81. Davies S, Ramsden DB: Huntington’s disease. Mol Pathol 2001;54:409–413.

    PubMed  CAS  Google Scholar 

  82. Ferrante RJ, Kowall NW, Richardson EP, Jr.: Proliferative and degenerative changes in striatal spiny neurons in Huntington’s disease: A combined study using the section Golgi method and calbindin d28k immunocytochemistry. J Neurosci 1991;11:3877–3887.

    PubMed  CAS  Google Scholar 

  83. Guidetti P, Charles V, Chen EY, Reddy PH, Kordower JH, Whetsell WO, Jr., Schwarcz R, Tagle DA: Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp Neurol 2001;169:340–350.

    Article  PubMed  CAS  Google Scholar 

  84. Klapstein GJ, Fisher RS, Zanjani H, Cepeda C, Jokel ES, Chesselet MF, Levine MS: Electrophysiological and morphological changes in striatal spiny neurons in r6/2 Huntington’s disease transgenic mice. J Neurophysiol 2001;86:2667–2677.

    PubMed  CAS  Google Scholar 

  85. Spires TL, Grote HE, Garry S, Cordery PM, Van Dellen A, Blakemore C, Hannan AJ: Dendritic spine pathology and deficits in experiencedependent dendritic plasticity in r6/1 Huntington’s disease transgenic mice. Eur J Neurosci 2004;19:2799–2807.

    Article  PubMed  Google Scholar 

  86. Spires TL, Grote HE, Varshney NK, Cordery PM, van Dellen A, Blakemore C, Hannan AJ: Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. J Neurosci 2004;24:2270–2276.

    Article  PubMed  CAS  Google Scholar 

  87. Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G: Missing pieces in the Parkinson’s disease puzzle. Nat Med 2010;16:653–661.

    Article  PubMed  CAS  Google Scholar 

  88. Freund TF, Powell JF, Smith AD: Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 1984;13:1189–1215.

    Article  PubMed  CAS  Google Scholar 

  89. Kramer ML, Schulz-Schaeffer WJ: Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 2007;27:1405–1410.

    Article  PubMed  CAS  Google Scholar 

  90. Revuelta GJ, Rosso A, Lippa CF: Neuritic pathology as a correlate of synaptic loss in dementia with Lewy bodies. Am J Alzheimers Dis Other Demen 2008;23:97–102.

    Article  PubMed  Google Scholar 

  91. Nikolaus S, Antke C, Muller HW: In vivo imaging of synaptic function in the central nervous system: I. Movement disorders and dementia. Behav Brain Res 2009;204:1–31.

    Google Scholar 

  92. McNeill TH, Brown SA, Rafols JA, Shoulson I: Atrophy of medium spiny i striatal dendrites in advanced Parkinson’s disease. Brain Res 1988;455:148–152.

    Article  PubMed  CAS  Google Scholar 

  93. Patt S, Gertz HJ, Gerhard L, Cervos-Navarro J: Pathological changes in dendrites of substantia nigra neurons in Parkinson’s disease: A Golgi study. Histol Histopathol 1991;6:373–380.

    PubMed  CAS  Google Scholar 

  94. Patt S, Gerhard L: A Golgi study of human locus coeruleus in normal brains and in Parkinson’s disease. Neuropathol Appl Neurobiol 1993;19:519–523.

    Article  PubMed  CAS  Google Scholar 

  95. Zaja-Milatovic S, Milatovic D, Schantz AM, Zhang J, Montine KS, Samii A, Deutch AY, Montine TJ: Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease. Neurology 2005;64:545–547.

    PubMed  CAS  Google Scholar 

  96. Deutch AY: Striatal plasticity in Parkinsonism: Dystrophic changes in medium spiny neurons and progression in Parkinson’s disease. J Neural Transm Suppl 2006:67–70.

  97. Stephens B, Mueller AJ, Shering AF, Hood SH, Taggart P, Arbuthnott GW, Bell JE, Kilford L, Kingsbury AE, Daniel SE, Ingham CA: Evidence of a breakdown of corticostriatal connections in Parkinson’s disease. Neuroscience 2005;132:741–754.

    Article  PubMed  CAS  Google Scholar 

  98. Ingham CA, Hood SH, Arbuthnott GW: Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res 1989;503:334–338.

    Article  PubMed  CAS  Google Scholar 

  99. Ingham CA, Hood SH, van Maldegem B, Weenink A, Arbuthnott GW: Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway. Exp Brain Res 1993;93:17–27.

    Article  PubMed  CAS  Google Scholar 

  100. Smith Y, Villalba RM, Raju DV: Striatal spine plasticity in Parkinson’s disease: Pathological or not? Parkinsonism Relat Disord 2009;15Suppl 3:S156–161.

    Article  PubMed  Google Scholar 

  101. Simic G, Kostovic I, Winblad B, Bogdanovic N: Volume and number of neurons of the human hippocampal formation in normal aging and alzheimer’s disease. J Comp Neurol 1997;379:482–494.

    Article  PubMed  CAS  Google Scholar 

  102. Terry RD: Alzheimer’s disease and the aging brain. J Geriatr Psychiatry Neurol 2006;19:125–128.

    Article  PubMed  Google Scholar 

  103. Hof PR, Cox K, Morrison JH: Quantitative analysis of a vulnerable subset of pyramidal neurons in alzheimer’s disease: I. Superior frontal and inferior temporal cortex. J Comp Neurol 1990;301:44–54.

    Article  PubMed  CAS  Google Scholar 

  104. Hof PR, Morrison JH: Quantitative analysis of a vulnerable subset of pyramidal neurons in alzheimer’s disease: II. Primary and secondary visual cortex. J Comp Neurol 1990;301:55–64.

    Article  PubMed  CAS  Google Scholar 

  105. Morrison JH, Hof PR: Life and death of neurons in the aging brain. Science 1997;278:412–419.

    Article  PubMed  CAS  Google Scholar 

  106. Bussière T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR: Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer’s disease: Stereologic analysis of prefrontal cortex area 9. J Comp Neurol 2003;463:281–302.

    Article  PubMed  CAS  Google Scholar 

  107. Akram A, Christoffel D, Rocher AB, Bouras C, Kövari E, Perl DP, Morrison JH, Herrmann FR, Haroutunian V, Giannakopoulos P, Hof PR: Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the ca 1 field: Relationship with the progression of Alzheimer’s disease. Neurobiol Aging 2008;29:1296–1307.

    Article  PubMed  CAS  Google Scholar 

  108. Ferrer I, Guionnet N, Cruz-Sanchez F, Tunon T: Neuronal alterations in patients with dementia: A Golgi study on biopsy samples. Neurosci Lett 1990;114:11–16.

    Article  PubMed  CAS  Google Scholar 

  109. Einstein G, Buranosky R, Crain BJ: Dendritic pathology of granule cells in Alzheimer’s disease is unrelated to neuritic plaques. J Neurosci 1994;14:5077–5088.

    PubMed  CAS  Google Scholar 

  110. Moolman DL, Vitolo OV, Vonsattel JP, Shelanski ML: Dendrite and dendritic spine alterations in Alzheimer models. J Neurocytol 2004;33:377–387.

    Article  PubMed  CAS  Google Scholar 

  111. de Ruiter JP, Uylings HB: Morphometric and dendritic analysis of fascia dentata granule cells in human aging and senile dementia. Brain Res 1987;402:217–229.

    Article  PubMed  Google Scholar 

  112. Swaab DF, Hofman MA, Lucassen PJ, Salehi A, Uylings HB: Neuronal atrophy, not cell death, is the main hallmark of Alzheimer’s disease. Neurobiol Aging 1994;15:369–371; discussion 379–380.

    Article  PubMed  CAS  Google Scholar 

  113. Scheff SW, Price DA, Schmitt FA, Mufson EJ: Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 2006;27:1372–1384.

    Article  PubMed  CAS  Google Scholar 

  114. Knowles RB, Wyart C, Buldyrev SV, Cruz L, Urbanc B, Hasselmo ME, Stanley HE, Hyman BT: Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer’s disease. Proc Natl Acad Sci U S A 1999;96:5274–5279.

    Article  PubMed  CAS  Google Scholar 

  115. Le R, Cruz L, Urbanc B, Knowles RB, Hsiao-Ashe K, Duff K, Irizarry MC, Stanley HE, Hyman BT: Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: Implications for neural system disruption. J Neuropathol Exp Neurol 2001;60:753–758.

    PubMed  CAS  Google Scholar 

  116. Urbanc B, Cruz L, Le R, Sanders J, Ashe KH, Duff K, Stanley HE, Irizarry MC, Hyman BT: Neurotoxic effects of thioflavin s-positive amyloid deposits in transgenic mice and Alzheimer’s disease. Proc Natl Acad Sci U S A 2002;99:13990–13995.

    Article  PubMed  CAS  Google Scholar 

  117. Tsai J, Grutzendler J, Duff K, Gan WB: Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nat Neurosci 2004;7:1181–1183.

    Article  PubMed  CAS  Google Scholar 

  118. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, et al.: Alzheimer-type neuropathology in transgenic mice overexpressing v717f beta-amyloid precursor protein. Nature 1995;373:523–527.

    Article  PubMed  CAS  Google Scholar 

  119. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L: Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc Natl Acad Sci U S A 1999;96:3228–3233.

    Article  PubMed  CAS  Google Scholar 

  120. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L: Highlevel neuronal expression of Ab 1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J Neurosci 2000;20:4050–4058.

    PubMed  CAS  Google Scholar 

  121. Wu CC, Chawla F, Games D, Rydel RE, Freedman S, Schenk D, Young WG, Morrison JH, Bloom FE: Selective vulnerability of dentate granule cells prior to amyloid deposition in pdapp mice: Digital morphometric analyses. Proc Natl Acad Sci U S A 2004;101:7141–7146.

    Article  PubMed  CAS  Google Scholar 

  122. Alpar A, Ueberham U, Bruckner MK, Seeger G, Arendt T, Gartner U: Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice. Brain Res 2006;1099:189–198.

    Article  PubMed  CAS  Google Scholar 

  123. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE: Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 2006;103:5161–5166.

    Article  PubMed  CAS  Google Scholar 

  124. Tackenberg C, Brandt R: Divergent pathways mediate spine alterations and cell death induced by amyloid-beta, wild-type tau, and r406w tau. J Neurosci 2009;29:14439–14450.

    Article  PubMed  CAS  Google Scholar 

  125. D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, Diamantini A, De Zio D, Carrara P, Battistini L, Moreno S, Bacci A, Ammassari-Teule M, Marie H, Cecconi F: Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci 2011;14:69–76.

    Article  PubMed  CAS  Google Scholar 

  126. Shahani N, Subramaniam S, Wolf T, Tackenberg C, Brandt R: Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of alzheimer’s disease-relevant tau constructs in organotypic hippocampal slices. J Neurosci 2006;26:6103–6114.

    Article  PubMed  CAS  Google Scholar 

  127. Darmopil S, Petanjek Z, Mohammed AH, Bogdanovic N: Environmental enrichment alters dentate granule cell morphology in oldest-old rat. J Cell Mol Med 2009;13:1845–1856.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Erik B. Bloss, John H. Morrison, Patrick R. Hof & Dara L. Dickstein

  2. Department of Geriatrics and Palliative Care, Mount Sinai School of Medicine, New York, NY, 10029, USA

    John H. Morrison, Patrick R. Hof & Dara L. Dickstein

  3. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Patrick R. Hof & Dara L. Dickstein

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  1. Erik B. Bloss
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  2. John H. Morrison
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  3. Patrick R. Hof
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  4. Dara L. Dickstein
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Correspondence to Dara L. Dickstein.

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Bloss, E.B., Morrison, J.H., Hof, P.R. et al. Influence of aging and neurodegeneration on dendritic spine morphology. Translat.Neurosci. 2, 49–60 (2011). https://doi.org/10.2478/s13380-011-0008-3

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  • DOI: https://doi.org/10.2478/s13380-011-0008-3

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